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Advances in psychiatric treatment (2009), vol. 15, 380–388 doi: 10.1192/apt.bp.107.004572
Early-onset dementia
ARTICLE
Kate Jefferies and Niruj Agrawal
Kate Jefferies is a consultant
in old age psychiatry at Farnham
Road Hospital, Guildford. She has
a special interest in early-onset
dementia and runs a specialist
service for early-onset dementia
in Guildford and Waverley. She
is also currently involved in the
future development of a Surreywide assessment service for
people with early-onset dementia.
Niruj Agrawal is a consultant
neuropsychiatrist at St George’s
Hospital London and an honorary
senior lecturer with St George’s,
University of London. He is
responsible for providing tertiary
care neuropsychiatry services for
the population of south-west London
and patients attending Atkinson
Morley Regional Neurosciences
Centre (St George’s Hospital) and the
Wolfson Neurorehabilitation Centre,
Wimbledon.
Correspondence Dr Niruj
Agrawal, Department of
Neuropsychiatry, St George’s
Hospital, London SW17 0QT, UK.
Email: Niruj.Agrawal@swlstg-tr.
nhs.uk
For a discussion of rare and unusual
dementias, see Gupta et al, pp.
364–372, this issue.
Prevalence, number of cases per 100 000 people
†
fig 1
380
summary
Dementia is is stereotypically associated with older
people. However, in a significant minority it can
affect people in their 40s and 50s, or even younger.
Currently there is a lack of awareness, even among
healthcare professionals, and there is a dearth of
appropriate services for such patients. Despite the
attention given to this condition by National Institute
for Health and Clinical Excellence guidelines, provi­
sion of specialist early-onset dementia services
in the UK remains patchy. Carers and patients
often find themselves being passed ‘from pillar
to post’ between psychiatry and neurology, and
also between adult, old age and liaison psychiatry.
The respon­si­bility for identifying available and
appropriate help is often left with carers. This leads
to unnecessary delays, causes undue distress to
patients and places an added burden on carers.
Declaration of interest
None.
Early-onset dementias are a fascinating group of
disorders that present challenges in diagnosis, management and service provision. It has become accepted practice that ‘early-onset’ refers to dementias
that occur before the age of 65 years.†
The ICD–10 definition of dementia is ‘a syndrome
due to disease of the brain, usually of a chronic or
progressive nature, in which there is disturbance of
multiple higher cortical functions, including memory,
thinking, orientation, comprehension, calculation,
learning capacity, language and judge­ment’ (World
Health Organization 1992: p. 45). ICD–10 also
states that the primary requirement for a diagnosis
of dementia is evidence of a decline in both memory
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140
120
100
80
60
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40
20
and thinking sufficient to impair activities of daily
living. However, it should be remem­bered that
dementias, particularly in younger people, often
present with symptoms other than memory decline
as the predominant feature.
Differences between young-onset
dementias and dementias in later life
Early-onset dementia is less common than dementia
in later life. The differential diagnosis is broader and
younger people are more likely to have a rarer form
of dementia. Both the diagnosis and the symptoms
of the condition can have a devastating impact on
patients, carers and their families. Younger people
are likely to have different needs and commitments
than older people. They are more likely to be in
work at the time of diagnosis, have dependent
family or children and have heavy financial
commitments (e.g. a mortgage). They are also likely
to be physically fit and active, and aware of their
problems. As a consequence, they are likely to feel
distressed and frustrated. Yet access to information
and support can be difficult and limited. Spouses
of patients with early-onset dementia have many
concerns, especially worries about financial and
health matters, a feeling of lack of support and
social isolation (Kaiser 2006).
Prevalence of early-onset dementia
In 1998, an estimated 18 500 people had early-onset
dementia in the UK (Harvey 1998). The disease was
more common in men than in women: in people
between 30 and 64 years of age there were 78.2
cases per 100 000 men and 56.4 cases per 100 000
women. Incidence increased sharply with age,
with two-thirds of patients aged 55 and over (Fig.
1). About a decade later, Knapp & Prince (2007)
reported a comparable prevalence, with of earlyonset dementias accounting for 2.2% of all people
with dementia in the UK. They calculated that there
are at least 15 034 people with early-onset dementia.
However, this estimate is based on the number of
referrals to services, and the true figure may be up
to three times higher.

Diagnosis of early-onset dementia
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0
30–34
35–39
40–44
45–49
Age, years
50–54
Prevalence of dementia by age (data from Harvey et al 1998).
55–59
60–64
Distribution of diagnosis
Comparison of Fig. 2 (a) and (b) shows that the
distribution of diagnoses of dementia differs
Early-onset dementia
2%
4%
Alzheimer’s disease
25%
31%
2% 3%
Vascular dementia
Alzheimer's disease
Vascular dementia
10%
Mixed Alzheimer's disease
and vascular dementia
Frontotemporal dementia
Alcohol-related dementia
4%
Dementia with Lewy bodies
17%
Other
12%
62%
Frontotemporal dementia
Parkinson’s disease
15%
Other
13%
(a)
fig 2
Dementia with Lewy bodies
(b)
(a) Distribution of diagnoses in young-onset dementia (data from Sampson et al 2004); (b) distribution of diagnoses of dementia occurring in later life (redrawn
from Knapp & Prince 2007, with kind permission of the Alzheimer’s Society).
dramatically between older and younger patients.
Alzheimer’s disease is the most common cause of
dementia in both groups, accounting for almost
two-thirds of cases in older people, but only a
third of cases in younger people. Frontotemporal
dementia occurs much more commonly in younger
than in older populations. Rarer causes of dementia
also occur with greater frequency in the younger
population.
Clinical approach to assessment
Assessment requires input from the multidisciplinary
team. Early diagnosis is essential for a number of
reasons: so that early treatment can be provided;
to enable the person and family to come to terms
with the illness; to allow early access to the correct
support; and so that appropriate plans for the future
can be made.
Clinically, the focus is on identifying early-onset
dementia accurately and on differentiating it from
illnesses that can also cause cognitive impairment
and mimic dementia. The differential diagnosis of
early-onset dementia includes various neurological
illnesses, psychiatric illnesses, traumatic brain injury
and drug misuse (Box 1).
Cognitive testing
Detailed neuropsychological testing is an important
component of the diagnostic process. It can reveal
the precise nature and location of the cognitive
deficits. Neuropsychological testing can also help in
teasing out whether there has been any progression
of dementia. Using a series of psychological tests,
the neuropsychologist establishes the cognitive
abilities of the person and compares them with the
person’s estimated best levels and with those for an
average person of the same age. Neuropsychological
assessment can also identify where a person’s abilities
are preserved so that they can be maximised.
Basic bedside testing is also helpful in confirming
the nature, degree and location of deficits. The
Mini Mental State Examination (MMSE) (Folstein
History
History should be obtained from the patient and
collateral information should be gathered from an
informant such as a family member. An informant’s
account is often the key to an accurate diagnosis.
Particular areas to concentrate on during historytaking are onset and evolution of symptoms, pattern
of deficits, fluctuations in mental state, past or
present neurological symptoms, current psychiatric
symptoms, past psychiatric symptoms, medical
history, family history, use of drugs and alcohol, and
risk assessment.
Advances in psychiatric treatment (2009), vol. 15, 380–388 doi: 10.1192/apt.bp.107.004572
Box 1 Differential diagnosis of early-onset
dementia
•
Delirium
•
Amnesic syndromes:
Korsakoff’s syndrome
anoxic brain damage
herpes simplex encephalitis
•
Mild cognitive impairment
•
Pseudodementia:
depression
dissociative
•
•
•
•
Traumatic brain injury
Neurological illness (e.g. normal-pressure
hydrocephalus, stroke, encephalitis, vasculitis, multiple
sclerosis)
General medical conditions (e.g. endocrine, B12
deficiency, systemic lupus erythematosus, sarcoidosis)
Drugs (e.g. alcohol, benzodiazepines)
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Jefferies & Agrawal
table 1
Bedside tests of frontal lobe function
Test
Example
Findings indicative of impairment
Verbal fluency
‘Name as many words as you can beginning with the letter “F”, any words
except names of people or places’
Fewer than 13 words a minute
Similarities
‘In what way are a banana and an orange alike?’
Inability to identify the similarity
Cognitive estimates
‘How tall is the tallest man?’
‘How fast can a horse gallop?’
Estimates will be inaccurate and often wildly wrong
Proverb interpretation
‘What do you understand by the saying “too many cooks spoil the broth”?’
Concrete (literal) not figurative responses
Luria hand sequence
Fist–edge–palm (the patient is asked to tap the table with a fist, open palm,
and side of open hand and to repeat the sequence as quickly as possible)
Inability to follow the sequence; perseveration
Conflicting instructions
‘Tap twice when I tap once, and tap once when I tap twice’
Copying the tapping pattern of examiner rather than
doing opposite despite clear instruction
Go/No-Go test
‘Tap once when I tap once. Do not tap when I tap twice’
Tapping twice when the examiner taps twice
1975) is the most widely used screening test for
cognitive impairment. It is short, easy to use,
has high interrater reliability and is useful for
monitoring illness progression. However, it is
insensitive to frontal lobe disorders, does not detect
focal cognitive deficits and is strongly influenced
by previous IQ and education. The Addenbrooke’s
Cognitive Examination (Mathuranath 2000) is a
more comprehensive screening instrument that
also tests frontal lobe functioning. It contains a
100-point test battery that assesses six cognitive
domains and takes about 15–20 min to complete.
It includes the MMSE.
Bedside tests of frontal lobe functioning are
described in Table 1.
Physical examination
Physical examination is important both in reaching
the diagnosis of the subtype of dementia and in
identifying any treatable comorbidity. The physical
examination is often normal in the early stages of
dementia but the presence of certain symptoms
and signs will arouse suspicion of a primary
neurological disorder. These include sudden onset
of symptoms, focal neurological findings early in the
illness, visual hallucinations, incontinence, ataxia
and early seizures.
In Alzheimer’s disease, patients are typically
physically well with no neurological signs in the early
stages. Later, there may be akinesia and rigidity.
In frontotemporal dementia, neurological signs are
also usually absent in the early stages. In later stages
of the disorder there may be evidence of primitive
reflexes, and with further disease progression there
may be akinesia and rigidity. Spontaneous features
of Parkinsonism are one of the core features of
dementia with Lewy bodies. Huntington’s disease
is evidenced by the presence of chorea and other
pyramidal symptoms. In Creutzfeldt–Jacob disease,
myoclonus and other extrapyramidal symptoms are
often present.
382
Further investigations
When arranging for further investigations the
priorities are to identify treatable causes of dementia
and to guide accurate diagnosis.
We suggest conducting the following investigations routinely: full blood count; erythrocyte
sedimen­tation rate; C-reactive protein; renal, liver
and thyroid function; syphilis serology; vitamin B12
and folate levels; bone profile; lipid profile; glucose;
structural neuroimaging by computed tomography
(CT) or magnetic resonance imaging (MRI). Electrocardiogram or chest X-ray should be carried out as
determined by the clinical presentation.
Structural neuroimaging should be carried out to
exclude other pathologies and to help establish the
subtype of dementia. Magnetic resonance imaging is
preferable, as CT may not show focal atro­phy well.
Functional imaging may be helpful in the detection of
focal brain dysfunction. Hexamethyl­propyleneamine
oxime (HMPAO) single-photon emission computed
tomography (SPECT) could help to differentiate
the subtype of dementia. Dopaminergic iodine123-radiolabelled SPECT can be used to confirm
suspected Lewy body dementia.
In atypical presentations, particularly when
dementia is rapidly progressive with features of
encephalopathy or focal neurological signs, patients
should be referred for neurological opinion; lumbar
puncture may be required. Additional investigations
such as HIV testing and CD4 count may be consid­
ered, depending on the clinical presentation.
Causes of early-onset dementia
The clinical presentations of the following diseases
generally do not differ between older and younger
populations.
Alzheimer’s disease
Alzheimer’s disease accounts for almost a third of
early-onset dementia cases. The typical presentation
Advances in psychiatric treatment (2009), vol. 15, 380–388 doi: 10.1192/apt.bp.107.004572
Early-onset dementia
of Alzheimer’s disease includes progressive episodic
(day-to-day) memory loss and visuospatial and
perceptual deficits, but well-preserved language and
social functioning. The posterior cortical variant of
the disease, with prominent impairment of parietal
lobe functions, is more common in younger people.
Alzheimer’s disease is more common in women
than men. Prevalence increases with increasing age.
The average duration of illness is 8 years. Alzheimer’s
disease mostly occurs as a sporadic disorder, even in
the younger population. However, inherited forms
are more likely in the younger population.
Inheritance is autosomal dominant. There are
many reported genetic mutations, but the three
most common ones are in the presenilin 1 gene on
chromosome 14, β-amyloid precursor protein on
chromosome 21 and the presenilin 2 gene on chromosome 1 (Schott 2002).
The preferred diagnostic criteria for Alzheimer’s
disease are those specified by the NINCDS–ADRDA
(National Institute of Neurological and Communicative Disorders and Stroke & Alzheimer’s Disease
and Related Disorders Association) (McKhann
1984) (Box 2).
The MRI scan in Fig. 3 illustrates the typical
findings in Alzheimer’s disease, namely dis­pro­
portionate bilateral atrophy of the hippocampi
(indicated by the white arrow).
Vascular dementia
Vascular dementia is the second most common
cause of dementia in younger people. Diagnosis is
based on the clinical picture, identification of risk
factors and brain imaging. The clinical presentation
is variable and depends on the site and extent of
the lesions. The preferred diagnostic criteria for
vascular dementia are the NINDS–AIREN (National
Institute of Neurological Disorders and Stroke &
Association Internationale pour le Recherche et
fig 3 MRI scan of Alzheimer’s disease. Reproduced with
kind permission of Professor Nick Fox, Institute of
Neurology, London.
Box 2 NINCDS–ADRDA criteria for the clinical diagnosis of probable
Alzheimer’s disease
•
•
•
Dementia established by clinical
examination and documented by the
MMSE, Blessed Dementia Scale or some
similar examination, and confirmed by
neuropsychological tests
Deficits in two or more areas of cognition
Progressive worsening of memory and
other cognitive functions
•
•
•
No disturbance of consciousness
Onset between ages 40 and 90, most
often after age 65
Absence of systemic disorders or other
brain diseases that in and of themselves
could account for the progressive deficits
in memory and cognition
(McKhann 1984)
l’Enseignement en Neurosciences) criteria (Roman
1993), which state that for a clinical diagnosis of
probable vascular dementia, both dementia and
cerebrovascular disease must be present and there
must be a relationship between the two disorders.
Vascular dementia has several syndromes:
••
••
••
••
multiple cortical infarcts leading to a stepwise
deterioration of cognitive functions
small vessel disease leading to a more insidious
decline of cognitive functioning
strategic infarcts – small cryptic strokes that cause
cognitive impairment
CADASIL (cerebral autosomal dominant arterio­
pathy with subcortical infarcts and leuko­
encephalo­pathy).†
CADASIL, an uncommon cause of young-onset
subcortical strokes and dementia, is caused by
mutations of the Notch3 gene on chromosome
19. Magnetic resonance imaging typically reveals
diffuse white matter lesions of the cerebral
hemispheres, especially the anterior temporal lobes
and external capsules (Fig. 4). Electron microscopy
of skin biopsies may reveal characteristic granular
osmophilic material.
For a discussion of CADASIL in
Advances see Taylor MH, Doody
GA (2008) CADASIL: a guide to
a comparatively unrecognised
condition in psychiatry. 14: 350–7.
Ed.
†
Frontotemporal dementia
Frontotemporal dementias occur more frequently in
the younger population. Men are more often affected
than women. The usual age at onset is between 45
and 65 years. The average duration of illness is 8
years. There is a positive family history in up to 50%
of patients.
There is an association between frontotemporal
dementia and motor neuron disease. The rate of
dementia in motor neuron disease is much higher
than expected, and indeed a significant minority
of patients with frontotemporal dementia develop
features of the disease. Up to 10% of patients with
motor neuron disease show features of dementia.
These individuals usually have an aggressive course
of illness.
The hallmark of frontotemporal dementia is
the early alteration in personality and social
Advances in psychiatric treatment (2009), vol. 15, 380–388 doi: 10.1192/apt.bp.107.004572
383
Jefferies & Agrawal
Behavioural form
The frontal variant primarily affects frontal lobes
and affected patients typically show symptoms
of frontal lobe dysfunction (Box 4) with relative
preservation of day-to-day memory. A typical MRI
scan of frontal lobe dementia is seen in Fig. 6.
Language forms
Primary progressive aphasia Patients have a pro­
gressive decline in their language with a relative
absence of other cognitive deficits. Speech is
non-fluent and effortful. Speech output becomes
increasingly difficult and in the later stages the
patient may become mute. Behavioural changes
may occur later in the disease. There is predominant
atrophy of the left perisylvian region.
Semantic dementia Patients have a variety of lanfig 4 MRI scan of CADASIL.
conduct, with relative preservation of memory,
perception, visuospatial skills and praxis. Although
presentations are variable and subtle, they are
often characterised by behavioural disturbance,
personality change, reduced motivation, reduced
empathy, impaired planning and judgement, and
speech and language problems. Box 3 shows clinical
criteria for frontotemporal dementia.
As the disease progresses, symptoms of frontal
lobe dysfunction may also become apparent. These
include behavioural rigidity, disinhibition, loss of
social skills and graces, fatuousness, emotional
lability, impulsivity, executive dysfunction, reduced
verbal fluency, hyperorality, and motor and verbal
perseveration.
Frontotemporal dementia can take a number of
forms (Fig. 5), which we describe below.
Box 3 Clinical criteria for frontotemporal dementia
1 The development of behavioural or
cognitive deficits manifested by either:
(a) early and progressive change in
personality, characterised by difficulty
in modulating behaviour, often
resulting in inappropriate responses or
activities; or
(b) early and progressive change in
language, characterised by problems
with expression of language or severe
naming difficulty and problems with
word meaning.
2 The deficits outlined in 1(a) or 1(b)
cause significant impairment in social or
occupational functioning and represent a
384
significant decline from a previous level
of functioning
3 The course is characterised by a gradual
onset and continuing decline in function
4 The deficits outlined in 1(a) or 1(b) are not
due to other nervous system conditions
(e.g. cerebrovascular disease), systemic
conditions (e.g. hypothyroidism), or
substance-induced conditions
5 The deficits do not occur exclusively
during a delirium
6 The disturbance is not better accounted
for by a psychiatric diagnosis (e.g.
depression)
(McKhann 2001)
guage difficulties, including naming difficulties,
impaired understanding of word meaning, and use
of substitute words. However, speech is fluent and
there is preservation of other cognitive domains.
Behavioural difficulties may emerge as the disease
progresses. Features of semantic dementia include
temporal lobe atrophy (of the left more than the
right). The characteristic feature is that atrophy
of the anterior temporal lobe is more pronounced
than that of the posterior temporal lobe (Fig. 7).
Dementia with Lewy bodies
The core features of Lewy body dementia include
progressive cognitive decline, fluctuating cogni­
tion, the presence of Parkinsonian symptoms, and
visual hallucinations that are typically recurrent,
well formed and detailed. Other features that are
highly suggestive of dementia with Lewy bodies
include rapid eye movement (REM) sleep behaviour
disorder, severe antipsychotic sensitivity and low
dopamine transporter uptake in the basal ganglia
demonstrated by SPECT or positron emission
tomography imaging (McKeith 2005).
A positive history of severe antipsychotic sensitivity suggests a diagnosis of dementia with Lewy
bodies. Lewy body dementia should be diagnosed
when dementia occurs before or concurrently with
Parkinsonism. Dementia that occurs in the context
of well-established Parkinson’s disease is best described as Parkinson’s disease dementia.
People with Lewy body dementia are extremely
sensitive to the side-effects of typical and atypical
antipsychotics. Approximately 50% of patients with
this type of dementia will have an adverse reaction
to the administration of antipsychotics.
Alcohol-related dementia
Heavy, prolonged alcohol use can cause damage to
the limbic structures and the frontal lobes, leading to
Advances in psychiatric treatment (2009), vol. 15, 380–388 doi: 10.1192/apt.bp.107.004572
Early-onset dementia
Frontotemporal dementia
Box 4 Symptoms of frontal lobe dysfunction
•
Change in social conduct
•
Change in behaviour
•
Behaviour inappropriate to the social situation
•
Lack of inhibitions
•
Impulsivity
•
Poor judgement
•
Inappropriate sexual behaviour
•
Repetitive or compulsive behaviours
•
Hyperorality
•
Self-neglect
•
Lack of insight
memory and executive impairments. Autobio­graph­
ical memory is often affected and confabulation can
occur. The memory loss is often static although may
improve following a period of abstinence. Imaging
may be non-specific or it may show generalised
cortical atrophy with a frontal preponderance.
Behavioural
Frontal variant
Language
Primary progressive aphasia
Semantic dementia
fig 5 Variants of frontotemporal dementia.
in the putamen and caudate head and cortical
hypersensitivity on fluid-attenuated inversion
recovery (FLAIR) sequences. Cerebral spinal fluid
proteins including 14-3-3 protein are elevated in
both sporadic and new variant CJD (the human
form of bovine spongiform encephalopathy).
New variant CJD commonly affects younger
people. The average age at onset is 26 years and
Huntington’s disease
The characteristic triad of clinical features in
Huntington’s disease are motor disorder, cognitive
disorder and emotional disorder. However, there
is variation between patients in the time of onset,
specific symptoms and the progression of illness.
Huntington’s disease is an autosomal dominant
disorder with complete penetrance caused by
expansion of the CAG trinucleotide repeat. Onset
is generally in middle life and the typical duration
of illness is 15–20 years. Diagnostic and predictive
testing is available.
Neuroimaging shows bilateral atrophy of the head
of the caudate nucleus and atrophy of the putamen and globus pallidus. Single-photon emission
computed tomography scans show cerebral hypo­
perfusion in the basal ganglia even before atrophy
is evident on MRI scan.
fig 6 MRI scan of frontal dementia, showing bifrontal atrophy and relative sparing of the
temporal lobes. Reproduced with kind permission of Professor Nick Fox, Institute of
Neurology, London.
Prion diseases
Creutzfeldt–Jakob disease (CJD) tends to occur in
middle life. It is rapidly progressive and often fatal
within 6 months. Prodromal insomnia, malaise
and depression are common. Myoclonus becomes
prominent as the disease progresses. Additional
symptoms include seizures, cerebellar ataxia,
cortical blindness and extrapyramidal symptoms.
Electroencephalogram (EEG) is grossly disturbed
and shows characteristic periodic triphasic wave
complexes. Computed tomography imaging is often
normal or shows non-specific atrophy. Magnetic
resonance imaging may show high signal changes
Advances in psychiatric treatment (2009), vol. 15, 380–388 doi: 10.1192/apt.bp.107.004572
fig 7 MRI scan of semantic dementia, showing disproportionate asymmetric atrophy of the
anterior left temporal lobe. Reproduced with kind permission of Professor Nick Fox,
Institute of Neurology, London.
385
Jefferies & Agrawal
the average duration of illness is 13 months. The
earliest symptoms are often psychiatric and include
depression, anxiety and agitation. There are no
distinctive changes on EEG. Magnetic resonance
imaging shows increased signal in the pulvinar.
Prion protein immunostaining is positive in
lymphoid tissues. The diagnosis can also be made
from a tonsillar biopsy.
Dementia in HIV infection and AIDS
Early features of HIV dementia include changes
in behaviour (particularly social withdrawal and
impaired activities of daily living), mood (apathy
and depression) and cognition. Patients complain
of forgetfulness, slowed thinking and poor
concen­tration. Neuropsychological tests reveal
abnormalities in spontaneity, motor speed and visual
memory, although language is often well preserved.
Neuro­l ogical signs include poor coordination,
loss of balance and tremor; later in the illness,
hyper­reflexia, dysdiadochokinesia, ocular pursuit
abnormalities, myoclonus and frontal lobe signs
may be observed. As the illness progresses there
is a global deterioration in cog­nitive functioning
and incontinence, with seizures, myoclonus and
mutism.
Dementia occurs in 7% of patients who are
HIV positive and 25% of patients with late-stage
AIDS (Mitchell 2004). The severity of the dementia
correlates with brain and cerebral spinal fluid levels
of HIV-1 RNA. HIV can affect any brain region but
the greatest concentrations of the virus are found in
the subcortical grey structures. Pathologically, there
is neuronal loss, small vessel disease and vacuolar
white matter lesions.
Mild cognitive impairments in HIV and AIDS
occur much more commonly than full-blown
dementias. Such impairments include deficits in
attending, slowed information processing and
reduced ability to retain new information. Subtle
changes are seen in 25–35% of people who are
HIV positive under the age of 40, and up to 90% of
people with AIDS who are aged over 50 (Mitchell
2004). Although these deficits are often minor, they
are not insignificant as they are associated with
a negative influence on survival, social problems,
unemployment and difficulty in driving.
table 2
Licensed uses of the anti-dementia drugs in the UK
Drug
Licensed use
Donepezil
Mild to moderate dementia in Alzheimer’s disease
Rivastigmine
Mild to moderate dementia in Alzheimer’s disease or Parkinson’s disease
Galantamine
Mild to moderate dementia in Alzheimer’s disease
Memantine
Moderate to severe dementia in Alzheimer’s disease
386
Management of early-onset dementia
Accurate diagnosis of early-onset dementia based
on comprehensive multidisciplinary assessment and
full investigation forms the basis for management. It
is important to identify treatable causes of dementia
and accurately diagnose underlying neurological or
psychiatric conditions. Longer-term support is vital
to help manage the cognitive, neuropsychiatric and
behavioural symptoms that often accompany these
disorders.
Management should encompass pharmacological
and non-pharmacological strategies. Nonpharmacological management strategies such as
psychoeducation, cognitive strategies such as mental
exercise, physical therapy and dietary treatment,
and drug therapies may be beneficial in reducing
the impact or slowing down the progression of the
disease. Medications may be needed for delusions,
hallucinations, and serious distress or danger from
behaviour disturbance or symptoms of depression.
Support packages should include appropriate day,
respite and intensive home care if required. Support
for families and carers is also required especially
in cases where there may be dependents such as
children.
Pharmacological interventions
Pharmacological management strategies include
anti-dementia drugs and other psychotropic drugs.
It is important to treat any comorbid medical or
psychiatric illnesses. The underlying degenerative
disorder should also be treated if appropriate.
In addition, vascular risk factors should be
addressed.
Anti-dementia drugs that are currently licensed
in the UK for patients of any age are donepezil,
rivastigmine, galantamine and memantine (Table
2). The available evidence base confirms that
the acetylcholinesterase inhibitors are effective
across the spectrum of Alzheimer’s disease (mild,
moderate and severe disease) and they also lead
to improvements in non-cognitive symptoms
(Burns 2005). Results of trials in other types of
dementia (vascular dementia, dementia with Lewy
bodies and Parkinson’s disease dementia) are also
positive, but the inhibitors are not currently licensed
in the UK for treatment of all of these conditions.
Acetylcholinesterase inhibitors should be prescribed
with caution in patients with sick sinus syndrome
or other supraventricular conduction abnormalities,
those who are susceptible to peptic ulcers, and in
asthma or chronic obstructive pulmonary disease.
Memantine, licensed in the UK for use in moderate
to severe Alzheimer’s disease, is an N-methyl-dasparate receptor antagonist, which may reduce
glutamate-mediated neuronal excitotoxicity.
Advances in psychiatric treatment (2009), vol. 15, 380–388 doi: 10.1192/apt.bp.107.004572
Early-onset dementia
The National Institute for Health and Clinical
Excellence (NICE) has produced guidelines on the
use of anti-dementia agents (National Institute for
Health and Clinical Excellence 2007) (Box 5).
box 5 NICE guidelines for Alzheimer’s disease
Donepezil, galantamine and rivastigmine are recommended for the adjunctive treatment of
moderate Alzheimer’s disease in those whose MMSE score is 10–20, under the following
conditions:
Antipsychotic agents
•
Symptoms that may respond to antipsychotic medication include physical aggression and psychotic
symptoms. They should be used for the shortest time
possible, at the lowest dose possible.
•
Antidepressants
Depression occurs frequently in early-onset
dementias. Symptoms of mood disturbance should
always be asked about. Selective serotonin reuptake
inhibitors are used as the first-line treatment because
of their favourable side-effect profile and because
an antidepressant with strong anticholinergic effects
may worsen cognition.
Psychological and non-pharmacological
interventions
Symptoms that may respond to non-pharmacological
interventions include mild depressive symptoms,
wandering and repetitive questioning. The ideal
environment for someone with dementia is one
that is constant, familiar and non-stressful. Other
therapies that have been shown to help in the
management of behavioural and psychological
symptoms in dementia include aromatherapy
(Holmes 2004), music therapy, recreation, bright
light therapy, behaviour therapy, reality orientation,
reminiscence therapy and art therapy (Douglas
2004; Woods 2004).
Alzheimer’s disease must be diagnosed in a specialist clinic. The clinic should also assess
cognitive, global and behavioural functioning, activities of daily living and likelihood of
adherence
treatment should be initiated by specialists, but continued by the general practitioner under
a shared care protocol
•
the carers’ views should be sought before and during the treatment
•
the patient should be reassessed every 6 months
•
the drug treatment should only continue if the MMSE remains at or above 10 and if it is
considered to have a beneficial effect on functioning and behaviour.
NICE does not recommend memantine for moderately severe to severe Alzheimer’s disease
except as part of clinical trials.
(National Institute for Health and Clinical Excellence 2007)
Younger people with dementia have different
needs than older people with the disease. General
dementia services are often inappropriate for use
by younger people and may not be able to meet
their needs. Age can often be a barrier to accessing
services, so in some parts of the UK younger people
may not be eligible to receive care from general
dementia services. We believe the best solution is
the development of regional specialist early-onset
dementia services in every area and for services to
be flexible; some people over the age of 65 may be
better suited to services for younger people, whereas
some people under the age of 65 may be better
catered for by the general dementia services.
Services for people with early-onset
dementia
Box 6 Organisations and further reading
The ongoing support and care of people with earlyonset dementia is complex and requires input from
a multidisciplinary team. Patients and their families
also benefit from the support offered by voluntary
organisations such as those listed in Box 6. However,
there are few specific statutory services in the UK
and there is limited awareness and understanding
of people who develop dementia at an early age,
thus making it difficult to access support. In the
absence of specific services, 38 referral pathways
and 4 separate gateways to specialist investigation
and care were identified in the city of Leeds in the
UK (Williams 2001). Another UK study reported
11 different referral pathways (Fuhrmann 1997).
Patients can be referred to two to five different
consultants sequentially, leading to significant
delays in diagnosis (Williams 2001). This is clearly
unsatisfactory service provision and causes high
rates of patient and carer dissatisfaction.
Organisations
Advances in psychiatric treatment (2009), vol. 15, 380–388 doi: 10.1192/apt.bp.107.004572
•
•
Alzheimer’s Society (www.alzheimers.org.uk)
Alzheimer’s Society’s information officer for younger
people with dementia (www.alzheimers.org.uk/
Younger_People_with_Dementia/index.htm)
•
Pick’s Disease Support Group (www.pdsg.org.uk)
•
CJD Support Network (www.cjdsupport.net)
•
The Lewy Body Society (www.lewybody.org)
Further reading
Hodges J (ed) (2001) Early-Onset Dementia: A
Multidisciplinary Approach. Oxford University Press.
Jefferies K, Agrawal N (2006) Early onset dementias.
CPD online, Royal College of Psychiatrists
(www.psychiatrycpd.co.uk/learningmodules/
earlyonsetdementias.aspx).
Murray M, Baldwin RC (eds) (2003) Younger People with
Dementia: A Multidisciplinary Approach. Taylor & Francis.
387
Jefferies & Agrawal
MCQ answers
1
2
3
a f a f a f
b f b t b f
c t c f c t
d f d f d f
e f e f e f
National recommendations
4
a f
b f
c t
d f
e f
5
af
bf
cf
dt
ef
Various recent publications have ratified the
need for specialist services for people with earlyonset dementia in the UK. The National Institute
for Health and Clinical Excellence & Social Care
Institute for Excellence (2006) joint guidelines state
that specialist multidisciplinary services allied to
existing dementia services should be developed for
the assessment, diagnosis and care of younger people
with dementia. The Royal College of Psychiatrists &
Alzheimer’s Society report (2006) states that there
should be a named person responsible for planning
services for younger people with dementia and a
named consultant to provide clinical input. They
suggest that for populations of half a million or more
a specialist multidisciplinary team is justified.
To adequately address the needs of these patients
and their carers there needs to be cooperation and
collaboration across all the relevant statutory and
voluntary services. Carers regularly report that they
would like to see better coordination of services and
to receive welfare advice, support and respite care.
However, it is often unclear how services should
be accessed, with subsequent delay in diagnosis,
treatment and provision of appropriate support.
References
Burns A, O’Brien J, Ames D (eds) (2005) Dementia (3rd edn). Hodder
Arnold.
Douglas S, James I, Ballard C (2004) Non-pharmacological interventions
in dementia. Advances in Psychiatric Treatment; 10: 171–7.
Folstein MF, Folstein SE, McHugh PR (1975) ‘Mini-mental state’. A practical
method for grading the cognitive state of patients for the clinician. Journal
of Psychiatry Research; 12: 189–98.
Fuhrmann R (1997) Early-onset dementia in Brighton, Hove and Lewes
Area: Prevalence and Service Needs. Alzheimer’s Society, Brighton
branch.
Knapp M, Prince M (2007) Dementia UK: The Full Report. Alzheimer’s
Society (http://www.alzheimers.org.uk/downloads/Dementia_UK_Full_
Report.pdf).
Mathuranath PS, Nestor PJ, Berrios GE, et al (2000) A brief cognitive test
battery to differentiate Alzheimer‘s disease and frontotemporal dementia.
Neurology; 55: 1613–20.
McKeith IG, Dickson DW, Lowe J, et al (2005) Diagnosis and management
of dementia with Lewy bodies: third report of the DLB Consortium.
Neurology; 65: 1863–72.
McKhann G, Drachman D, Folstein M, et al (1984) Clinical diagnosis of
Alzheimer’s disease: report of the NINCDS–ADRDA Work Group under
the auspices of Department of Health and Human Services Task Force on
Alzheimer’s Disease. Neurology; 34: 939–44.
McKhann G, Albert M, Grossman M, et al (2001) Clinical and pathological
diagnosis of frontotemporal dementia: report of the Work Group on
Frontotemporal Dementia and Pick’s Disease. Archives of Neurology; 58:
1803–9.
Mitchell AJ (2004) Neuropsychiatry and Behavioural Neurology Explained:
Diseases, Diagnosis and Management. W.B. Saunders.
National Institute for Health and Clinical Excellence, Social Care Institute
for Excellence (2006) Dementia: Supporting People with Dementia and
Their Carers in Health and Social Care. NICE.
National Institute for Health and Clinical Excellence (2007) Alzheimer’s
Disease – Donepezil, Galantamine, Rivastigmine (review) and Memantine.
NICE.
Roman GC, Tatemichi TK, Erkinjuntti T, et al (1993) Vascular dementia:
diagnostic criteria for research studies. Report of the NINDS–AIREN
International Workshop. Neurology; 43: 250–60.
Royal College of Psychiatrists, Alzheimer’s Society (2006) Services for
Younger People with Alzheimer’s Disease and Other Dementias (Council
Report CR135). Royal College of Psychiatrists.
Sampson EL, Warren JD, Rossor MN (2004) Young onset dementia.
Postgraduate Medical Journal; 80: 125–39.
Schott JM, Fox NC, Rossor MN (2002) Genetics of the dementias. Journal
of Neurology, Neurosurgery and Psychiatry; 73 (suppl II): ii27–31.
Williams T, Dearden AM, Cameron IH (2001) From pillar to post – a study
of younger people with dementia. Psychiatric Bulletin; 25: 384–7.
Harvey R (1998) Young Onset Dementia: Epidemiology, Clinical Symptoms,
Family Burden, Support and Outcome. Dementia Research Group.
World Health Organization (1992) The ICD–10 Classification of Mental and
Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines.
WHO.
Holmes C, Ballard C (2004) Aromatherapy in dementia. Advances in
Psychiatric Treatment; 10: 296–300.
Woods B (2004) Invited commentary on: Non-pharmacological interventions
in dementia. Advances in Psychiatric Treatment; 10: 178–9.
MCQs
1 The prevalence of early-onset dementia in
the UK is:
a 5000–10 000
b 10 000–15 000
c 15 000–20 000
d 20 000–25 000
e 25 000–30 000.
2 The most common cause of dementia in
people under the age of 65 years is:
a alcohol-related dementia
b Alzheimer’s disease
c dementia with Lewy bodies
d frontotemporal dementia
e vascular dementia.
388
Kaiser S, Panegyres PK (2006) The psychosocial impact of young onset
dementia on spouses. American Journal of Alzheimer’s Disease and Other
Dementias; 21: 398–402.
3 Among people with dementia, more
younger people than older people have:
a Alzheimer’s disease
b dementia with Lewy bodies
c frontotemporal dementia
d mixed dementia
e vascular dementia.
5 The following is not a test of frontal lobe
function:
a cognitive estimates
b Luria sequence
c proverb interpretation
d serial sevens
e verbal fluency.
4 Of people with frontotemporal dementia,
the proportion with a positive family
history of the disease is:
a 0%
b 25%
c 50%
d 75%
e 100%.
Advances in psychiatric treatment (2009), vol. 15, 380–388 doi: 10.1192/apt.bp.107.004572